Nicole Hardy

PALB2 c.3106G>C (p.Val1036Leu) in a familial cancer setting suggesting potential pathogenicity

The case is a woman in her 60s with a heterozygous germline variant in PALB2 (c.3106G>C, p.Val1036Leu) who developed ovarian cancer. Tumour somatic analysis revealed a 24.7% loss of heterozygosity, commonly associated with homologous recombination deficiency. No other pathogenic DNA damage repair gene mutations were identified, although ATR amplification was observed. The proband has four siblings, all of whom tested positive for the PALB2 c.3106G>C variant. Both of her brothers were diagnosed with prostate cancer. One of her sisters was diagnosed with breast cancer at age 62, while the other sister has no cancer history. The patient’s two children have not been tested and have no reported history of cancer. Her father had prostate cancer at age 67 and died due to melanoma at age 75. No history of cancer was found on her mother’s side. Segregation analysis of the PALB2 c.3106G>C variant with multiple cancer diagnoses suggests a pathogenic role.